The crystal structure of Thermus thermophilus elongation factor G without guanine nucleotide was determined to 2.85 A. This GTPase has five domains with overall dimensions of 50 × 60 × 118 A. The GTP binding domain has a core common to other GTPases with a unique subdomain which probably functions as an intrinsic nucleotide exchange factor. Domains I and II are homologous to elongation factor Tu and their arrangement, both with and without GDP, is more similar to elongation factor Tu in complex with a GTP analogue than with GDP. Domains III and V show structural similarities to ribosomal proteins. Domain IV protrudes from the main body of the protein and has an extraordinary topology with a left‐handed cross‐over connection between two parallel beta‐strands.

The pyruvate dehydrogenase multienzyme complex (M r of 5-10 million) is assembled around a structural core formed of multiple copies of dihydrolipoyl acetyltransferase (E2p), which exhibits the shape of either a cube or a dodecahedron, depending on the source. The crystal structures of the 60-meric dihydrolipoyl acyltransferase cores of Bacillus stearothermophilus and Enterococcus faecalis pyruvate dehydrogenase complexes were determined and revealed a remarkably hollow dodecahedron with an outer diameter of Ϸ237 Å, 12 large openings of Ϸ52 Å diameter across the fivefold axes, and an inner cavity with a diameter of Ϸ118 Å. Comparison of cubic and dodecahedral

Essentially all MSUD mutations in human E1b can be explained on the basis of the structure, with the severity of the mutations for the stability and function of the protein correlating well with the severity of the disease for the patients. The suggestion is made that small molecules with high affinity for human E1b might alleviate effects of some of the milder forms of MSUD.